ABSTRACT

Context Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter
(PAC) have been limited by small sample size. Some nonrandomized studies suggest
that PAC use is associated with increased morbidity and mortality.

Objective To estimate the impact of the PAC device in critically ill patients.

Data Sources MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (1988-2005),
the National Institutes of Health ClinicalTrials.gov database, and the US
Food and Drug Administration Web site for RCTs in which patients were randomly
assigned to PAC or no PAC were searched. Results from the ESCAPE trial of
patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart
catheter, catheter, and Swan-Ganz.

Study Selection Eligible studies included patients who were undergoing surgery, in the
intensive care unit (ICU), admitted with advanced heart failure, or diagnosed
with acute respiratory distress syndrome and/or sepsis; and studies that reported
death and the number of days hospitalized or the number of days in the ICU
as outcome measures.

Data Synthesis In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment
strategies varied among trials. A random-effects model was used to estimate
the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes
and intravenous vasodilators. The combined OR for mortality was 1.04 (95%
confidence interval [CI], 0.90-1.20; P = .59).
The difference in the mean number of days hospitalized for PAC minus the mean
for no PAC was 0.11 (95% CI, −0.51 to 0.74; P = .73).
Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95%
CI, 1.19-2.12; P = .002) and intravenous
vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P<.001).

Conclusions In critically ill patients, use of the PAC neither increased overall
mortality or days in hospital nor conferred benefit. Despite almost 20 years
of RCTs, a clear strategy leading to improved survival with the PAC has not
been devised. The neutrality of the PAC for clinical outcomes may result from
the absence of effective evidence-based treatments to use in combination with
PAC information across the spectrum of critically ill patients.

Figures in this Article

The pulmonary artery catheter (PAC) is used to diagnose various diseases
and physiological states, monitor the progress of critically ill patients,
and guide the selection and adjustment of medical therapy.1 The
PAC is often considered a cornerstone of critical care and a hallmark of the
intensive care unit (ICU).2 Approximately 1
million PACs are used annually in the United States.3 However,
despite widespread use of these devices, there are conflicting data about
their utility. The majority of nonrandomized studies in critically ill patients
have suggested that the PAC is associated with increased morbidity and mortality.4 Conversely, some nonrandomized studies have shown
improved quality of life when the PAC was used to direct a specific therapeutic
approach.5- 7

Since the mid-1980s, randomized clinical trials (RCTs) have been conducted
to evaluate the efficacy of the PAC. However, none of these trials have been
persuasive individually, because they are limited by small sample sizes in
heterogeneous populations. Ivanov et al performed 2 meta-analyses on PAC use
through 1996.8,9 One study focused
on mortality from 16 RCTs of the PAC8 and the
other focused on major morbidity from 12 RCTs9;
however, neither study restricted the randomization specifically to catheter
vs no catheter use. There was no difference found in mortality, but there
was a statistically significant difference in major morbidity, which was defined
separately for each organ system.8,9

Despite the overwhelmingly negative tenor of the literature, clinicians
continue to use the PAC in ICUs based on personal experience and the belief
that careful monitoring will improve decision making and clinical outcomes.
To provide a broad perspective for the recently completed ESCAPE trial,10 in which patients with advanced heart failure were
randomized to the PAC or clinical assessment alone, we performed a meta-analysis
of 13 recently published clinical trials testing the safety and efficacy of
the PAC.

METHODS

Study Search

We searched MEDLINE (1985-2005), the Cochrane Controlled Trials Registry
(1988-2005), the National Institutes of Health ClinicalTrials.gov database,
and the US Food and Drug Administration Web site (http://www.fda.gov) for reports of articles pertaining to the PAC. The MEDLINE search
results included all articles yielded by other search methods. The search
terms used were pulmonary artery catheter, right heart catheter, catheter,
and Swan-Ganz.

For the MEDLINE search, we used the term pulmonary
artery catheter as a keyword. We then searched the subject headings catheterization, Swan-Ganz, and pulmonary artery catheter. The search was limited to articles
that were written in English, included only human beings, and published between
1985 and 2005. These citations were then manually searched to identify articles
that were RCTs, systematic reviews, prospective cohort studies, or editorial
letters and comments. The references from the citations were also searched
to identify additional RCTs.

Eligibility and Data Abstraction

We reviewed references identified by the search method specified above.
Additional references were identified by manually searching the bibliographies
of these articles. These citations were included in our meta-analysis. We
included trials if the randomization scheme included groups that assigned
patients to treatment guided by the PAC or treatment without the PAC. We only
included trials if they reported death and number of days hospitalized or
the number of days in the ICU as outcome measures. Studies were excluded if
the randomization scheme did not specify groups as PAC or no PAC, if patients
were not randomized to a conventional PAC, if investigators combined randomized
and nonrandomized groups when reporting outcomes, or if there were no outcome
data on death or hospitalizations.

Eligibility assessment and data abstraction were performed independently
in an unblinded standardized manner by 2 reviewers (M.R.S. and V.H.). Abstracted
data included eligibility criteria, baseline characteristics, interventions,
outcomes, and methodological quality. The outcome of interest was the number
of deaths from any cause and the number of days hospitalized. Trial methodological
quality was assessed by abstracting reported use of intention-to-treat analysis
and reported allocation generation and allocation concealment. Disagreements
between reviewers were resolved by consensus.

Data Analysis

Random-effects models were used for the meta-analysis of both mortality
and days hospitalized. Mortality was summarized by odds ratio (OR) with 95%
confidence intervals (CIs). Days hospitalized were summarized as the difference
in mean number of days. The measures were combined using an empirical Bayes
random-effects estimator,11 which also provides
an estimate of heterogeneity. The calculations were performed by using FAST*PRO
software version 1.80.12P<.05 was considered statistically significant.

Some of the studies had zero deaths in a particular group, which is
problematic for conventional meta-analysis methods. Meta-regression analysis
is an alternative method of estimating the pooled OR. Based on the assumption
used in standard meta-analysis, we assumed that the OR for mortality remained
constant across studies, except for some additional random variation. The
model was fitted using a logistic-normal model as implemented in EGRET for
Windows.13 These results were used as a check
on the empirical Bayes estimator.

RESULTS

Search Results

We identified 2305 articles with the subject headings catheterization, Swan-Ganz, or pulmonary artery catheter (Figure 1).
We limited our analysis to articles that were written in English, included
only human beings, and were published between 1985 and 2005, which yielded
1715 articles. We manually searched these citations and identified 11 RCTs
evaluating the PAC that met the prespecified criteria. In addition, we included
2 recently published trials. The first trial, Evaluation of the Clinical Care
and Cost Effectiveness of Pulmonary Artery Flotation Catheters in Intensive
Care (PAC-Man), was conducted in England and completed in March 2004.14 The second trial, the ESCAPE trial,10 was
presented at the American Heart Association meeting on November 9, 2004.

Figure 1. MEDLINE Articles Evaluated for Inclusion
in the Meta-analysis

Qualitative Findings

In total, 5051 patients were randomized into the 13 trials included
in our meta-analysis.10,14- 25 Eight
studies focused on patients undergoing major general, abdominal, vascular,
or orthopedic surgery.15- 18,20- 22,24 These
trials included 2667 (52.8%) of 5051 patients in the meta-analysis. Three
studies evaluated patients admitted to the ICU who were diagnosed with sepsis
or acute respiratory distress syndrome.19,23,25 These
trials included 910 patients (18.0%) of the meta-analysis study population.
Only 1 study, ESCAPE,10 focused primarily on
patients with advanced heart failure.

Five studies15,17,19,23,25 did
not require investigators to achieve specific hemodynamic targets. The protocols
of these studies called for clinicians to use their own judgment in assessing
therapeutic goals and designing treatment strategies.

In contrast, 2 studies10,16 clearly
outlined hemodynamic targets but did not specify which therapies should be
selected to achieve these goals. The protocol of the ESCAPE trial10 encouraged the use of vasodilators and diuretics
and discouraged inotropes but did not mandate use of these drugs.

The 5 most specific protocols focused on the surgical population.18,20- 22,24 These
trials outlined treatment strategies to achieve specific hemodynamic goals.
A summary of fluids and therapies used in the 13 trials is shown in Table 2.

Quantitative Findings. Overall, there was a
significantly higher rate of use of vasodilator agents in patients randomly
assigned to PAC (OR, 2.35; 95% CI, 1.75-3.15; P<.001).
In addition, use of inotropes was also significantly higher in patients randomly
assigned to PAC (OR, 1.58; 95% CI, 1.19-2.12; P = .002).

The meta-analysis of death in the 13 RCTs demonstrated that the PAC
did not significantly increase mortality. More importantly, the use of the
PAC also did not improve survival (OR, 1.04; 95% CI, 0.90-1.20; P = .59) (Figure 2).

Figure 2. Odds Ratio (PAC vs No PAC) for Mortality
of RCTs Evaluating the Safety and Efficacy of the PAC

In addition, the meta-analysis of the number of days hospitalized showed
that the PAC did not have a significant impact on this end point (mean for
PAC − mean for no PAC, 0.11 days; 95% CI, −0.51 to 0.74; P = .73) (Figure
3).

Figure 3. Mean Difference in the Average Number
of Days Hospitalized in PAC Randomized Controlled Trials (Mean for PAC −
Mean for No PAC)

COMMENT

Our meta-analysis of 13 RCTs evaluating the safety and efficacy of the
PAC demonstrates that use of the catheter neither improves outcomes in critically
ill patients nor increases mortality or days in hospital. This provides a
broader confirmation of the recent results of the ESCAPE trial,10 which
showed that the routine use of the PAC in patients with advanced heart failure
did not reduce or increase death or days in hospital.

PAC: A Diagnostic Tool

Previous clinical trials have evaluated the PAC as an intervention,
although it is only a diagnostic tool, similar to a chest radiograph or an
echocardiogram. To expect a diagnostic device to increase survival may be
unrealistic unless there is a therapeutic intervention associated with it
that improves outcomes. Our meta-analysis emphasizes the lack of consensus
about the goals of therapy in critically ill populations, the paucity of standard
guidelines on how to use the PAC, and the dearth of therapies that have met
modern criteria for evidence, which provide clinical benefit in acutely ill
populations.

Use of the PAC in Different Populations

The PAC may be used differently in the spectrum of critical illnesses.
Because the role of the PAC in different disease states varies, the catheter
may benefit some patients and harm others. The specific role the device plays
in treating patients may be a factor in determining its ultimate impact on
clinical outcomes. For example, in the ICU and surgical populations, the focus
of the PAC is on diagnosis of volume and perfusion status and the selection
and titration of drugs. In contrast, in the heart failure population, the
PAC is used not only to diagnose volume and perfusion status and titrate therapy,
but also to refine drug combinations and select equivalent oral doses of intravenous
medications. Because the use of the PAC may vary by disease state, combining
the results of different trials may not give an accurate estimate of the impact
of the device in specific patient populations. However, none of the individual
trials included in our meta-analysis showed a significantly positive effect
of the PAC on outcomes, so heterogeneity of response as an explanation for
the neutral results would have to be within each trial. We are unable to address
this issue because we do not have the individual patient data.

Therapies Associated With the PAC

Another potential reason that the results of our meta-analysis were
neutral may be that use of the PAC increased the accuracy of diagnosis, potentially
leading to increased survival, but that hemodynamic data also triggered use
of therapies that worsened outcomes. Four studies included in our analysis
presented information on how frequently intravenous inotropes and vasodilators
were used.10,23- 25

It may be that inotropes and vasodilators were used more frequently
in patients who received the PAC because objective hemodynamic goals were
present. There are few data, and no RCT data, that show either class of drugs
improves outcomes in acutely ill patients. In fact, the use of inotropic agents
and some vasodilators have been associated with increased morbidity and mortality
in the advanced heart failure population.26,27 In
addition, there is little evidence from RCTs to support the use of fluid loading,
blood transfusions, or intravenous vasodilators to achieve hemodynamic goals.28 Although use of the PAC may have allowed physicians
to diagnose clinical and hemodynamic status more accurately, it may have also
triggered the use of drugs that ultimately worsened outcomes.

Quality of Hemodynamic Data

Quality of hemodynamic data is also a critical factor in determining
the impact of the device on clinical outcomes. Eleven studies in our analysis
did not include a protocol for interpretation of hemodynamic wave forms. Thus,
there may have been inaccuracies in the hemodynamic data, which had an impact
on morbidity and mortality. In addition, only the ESCAPE trial required study
nurses to undergo formal training in hemodynamic waveform interpretation.
Without standard protocols for the PAC, there may have been errors in gathering
hemodynamic data, which may have ultimately affected clinical outcomes.

Hemodynamic Targets: The Wrong Surrogates?

Although many of the studies included in our meta-analysis outlined
specific hemodynamic goals, there are few definitive data to support the use
of any hemodynamic target. The decision to optimize filling pressures in the
ESCAPE trial was based mostly on the positive results of single-center, nonrandomized
studies using these targets.29,30 In
contrast, there are few data, even from nonrandomized studies, to support
maximizing cardiac index and oxygen delivery.31 It
may be that the observed neutral effect of the PAC was because investigators
were targeting drugs, fluid, and blood replacement to the wrong end points.

Ongoing Randomized Studies

We identified 1 additional unpublished trial evaluating the safety and
efficacy of the PAC. The Fluids and Catheter Treatment Trial focused on 1000
patients with acute respiratory distress syndrome.32,33 Patients
were randomized in a 2 × 2 factorial design to a liberal vs
conservative fluid treatment strategy and to therapy guided by a PAC or central
venous catheter. The primary end point was death at 60 days. The investigators
outlined specific hemodynamic goals and treatment strategies for the use of
inotropes, vasopressors, fluids, and diuretics. The trial was started in 2001
but was suspended by the Office for Human Protections From Research32 for questions about the ethics of the protocol. After
extended review by external consultants, the trial was restarted in 2002 with
no major revisions to the protocol.

Future Studies

The overview by Ivanov et al9 suggests
that nonfatal end points may be improved by disease-specific targeting of
therapy and the ESCAPE trial10 suggested the
possibility of quality of life improvement. Future trials should look at alternate
clinical end points, particularly symptom status. Furthermore, given the absence
of harm for major clinical end points, renewed emphasis should be placed on
the development of novel therapies that might be effective when coupled with
the diagnostic information obtained from the PAC.

Conclusions

During the past 60 years, the PAC has evolved from a simple diagnostic
tool to a device that is used for monitoring and determining goal-directed
therapy. Our meta-analysis shows that despite the widespread acceptance of
the PAC, use of this device across a variety of clinical circumstances in
critically ill patients does not improve survival or decrease the number of
days hospitalized. The patients included were those in whom physicians had
clinical equipoise about the use of the PAC. That is, clinicians were uncertain
about the use of the PAC before they randomized patients.

Although our results suggest that the PAC should not be a standard of
care, all of the trials excluded patients in whom clinicians thought a PAC
was required for treatment. Thus, it is possible that patients who are outside
the boundaries of these trials, such as those who are evaluated for heart
and lung transplantation, derive benefit from the PAC. However, these results
suggest that the PAC should not be used for the routine treatment of patients
in the ICU, patients with decompensated heart failure, or patients undergoing
surgery until or unless effective therapies can be found that improve outcomes
when coupled with this diagnostic tool.

Funding/Support: This meta-analysis was funded
by the Duke Clinical Research Institute.

Role of the Sponsor: With the exception of
the ESCAPE trial, the Duke Clinical Research Institute did not participate
in the design and conduct of the study, in the collection, analysis, and interpretation
of the data, or in the preparation, review, or approval of the manuscript.

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